Gender gap in risk factor control of coronary patients far from closing: results from the European Society of Cardiology EUROASPIRE V registry

Abstract

Aims

This study aims to provide an overview on contemporary gender differences in the risk factor control of coronary heart disease (CHD) patients.

Methods and results

Analyses were based on the cross-sectional ESC (European Society of Cardiology) EORP (EurObservational Research Programme) EUROASPIRE V (European Survey of Cardiovascular Disease Prevention and Diabetes) survey including data on CHD patients across 27 European countries. Men and women between 18 and 80 years old, hospitalized for a first or recurrent coronary event were included in the study. Data were available for 8261 patients of which 25.8% women. Overall, women had a worse risk factor control compared with men. Whereas women were more likely to be non-smokers (79.3% vs. 87.2%; P < 0.001), they were less likely to reach recommended levels of physical activity (36.8% vs. 27.5%; P < 0.001), and they were less likely to be non-obese (65.1% vs. 54.3%; P < 0.001). There is indication that risk factors such as smoking behaviour and obesity differed depending on country income level. No gender differences could be observed in blood pressure on target (P > 0.05). Moreover, a lower proportion of women reached low-density lipoprotein cholesterol (LDL-C) target levels (31.4% vs. 22.1%; P < 0.001), and they were less likely to reach glycated haemoglobin (HbA1c) targets if having self-reported diabetes (56.7% vs. 48.6%; P < 0.001).

Conclusion

The risk factor control of CHD women is substantial worse compared with men despite little gender differences in cardiovascular medication intake. Further actions are needed to increase the awareness of the worse risk factor control in female CHD patients.

Introduction

Cardiovascular disease (CVD) remains the leading cause of mortality and morbidity across Europe, with about 47% of women and 39% of men dying from CVD.¹ In response, the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Joint European Societies—JES) provide regularly updated recommendations to prevent CVD by guiding healthcare professionals in their daily clinical practice.^1,2 The main objectives of these guidelines are to reduce CVD mortality and morbidity, to reduce events, and to improve patients’ quality of life.² Despite substantial efforts to promote the importance of risk factor management in patients with coronary heart disease (CHD), an unacceptably large amount of patients do not reach the recommended risk factor targets.^3–5 Previous large-scale studies reporting on risk factor management suggest an even worse risk factor profile among female patients, despite gender-neutral recommendations.^6–8 Women were less likely to reach adequate levels of physical activity, they were more frequently obese, and they were more likely to have a history of diabetes.^6,8 Women were also less likely to reach risk factors targets for glycated haemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C). In contrast, women were more likely to be non-smokers.^6,8 This gender gap in risk factor occurrence is of paramount interest, especially since risk factors like smoking and diabetes may have an even more detrimental effect in female patients.^9,10 The aim of this study was to provide an overview on contemporary gender differences in risk factor control of CHD patients across Europe. Analyses were based on data from the latest EUROASPIRE V survey. A particular focus is given to the stratification of risk factors by country income level, to investigate whether there are gender differences according to gross national income.

Methods

The cross-sectional ESC (European Society of Cardiology) EORP (EurObservational Research Programme) EUROASPIRE V survey was conducted in 2016–2017 to evaluate the implementation of the Joint European Societies Guidelines (2016) on Cardiovascular Disease Prevention in daily clinical practice² in coronary patients. Detailed information on the study design and methodology has been reported elsewhere.⁴ Within each country, at least one geographical area with a defined population was selected. A total of 131 centres were included, covering 27 countries (Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Egypt, Finland, Germany, Greece, Ireland, Italy, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, The Netherlands, Poland, Portugal, Romania, Russian Federation, Serbia, Slovenia, Spain, Sweden, Turkey, Ukraine, and the UK). Consecutive patients (men and women), between 18 and 80 years old at the time of identification, were retrospectively identified from diagnostic registers, hospital discharge lists, or other sources. Patients eligible for inclusion had to be hospitalized for an elective or emergency coronary artery bypass grafting (CABG), an elective or emergency percutaneous coronary intervention (PCI), an acute myocardial infarction (AMI; ICD-10 I21), or an acute myocardial ischaemia (ICD-10 I20) at least 6 months and not more than 2 years prior to the date of the study visit. Local research ethics committee approval for each participating centre was obtained. Written informed consent was completed by each participant. Data were submitted to the data management centre EURObservational Research Program (EORP), ESC, Sophia-Antipolis, France. Data collection was undertaken by centrally trained research staff using standardized methods and instruments. Information on patient’s demographics, risk factor profile, and disease management was obtained from medical records, patient interviews, medical examination, and venous (fasting) blood sample using standardized methods and instruments. Blood samples were centrally analysed by the Biochemistry Laboratory in the National Institute of Health and Welfare (Helsinki, Finland).

Variables and definitions

The Sixth Joint European Society guidelines (2016) were used to define the risk factor targets.² Current smoking was defined as self-reported smoking and/or a breath carbon monoxide >10 ppm. Smoking cessation was defined as non-smoking at time of the interview among those who smoked in the month before the recruiting event. A recommended level of physical activity was defined as regularly physical activity for at least 30 min, five times or more a week. Obesity was defined as a body mass index (BMI) ≥30 kg/m². Blood pressure was measured twice on the right upper arm in a sitting position using an automatic digital sphygmomanometer. The mean of both measurements was used for analyses. Targets for blood pressure were set at systolic/diastolic blood pressure (SBP/DBP) <140/90 mmHg (<140/85 mmHg in patients with diabetes). ‘Controlled hypertension’ was used to indicate blood pressure levels on target in patients treated with anti-hypertensive medication. Venous (fasting) blood samples were taken to analyse LDL-C, high-density lipoprotein cholesterol (HDL-C), and HbA1c levels. The LDL-C was calculated according to the Friedewald’s formula.¹¹ Targets for LDL-C levels was defined as an LDL-C <1.8 mmol/L. ‘Controlled dyslipidaemia’ was used to indicate LDL-C levels on target in patients treated with lipid-lowering drugs. HbA1c level targets were defined as <7% in patients with self-reported diabetes and <6.5% in patients without diabetes. Previous hospitalization for stroke, heart failure, CABG/PCI, and peripheral artery disease (PAD) were defined as ever being hospitalized for a stroke, heart failure, CABG/PCI, and PAD, respectively. Information on cardiovascular medication intake was based on medication use at the time of the study visit (patients were asked to bring their medication with them during study visit).

Educational level was divided into three categories: primary education (no formal school, less than primary school, or primary school completed), secondary education (secondary school completed, high school completed, or intermediate between secondary level), and high education (College/University completed or post-graduate degree). In addition, countries were grouped in two categories according to their gross national income per capita using the World Bank Atlas method¹²: high-income countries (Belgium, Croatia, Czech Republic, Finland, Germany, Greece, Ireland, Italy, Latvia, Lithuania, Poland, Portugal, Slovenia, Spain, Sweden, The Netherlands, and UK) and middle-income countries (Bosnia and Herzegovina, Bulgaria, Egypt, Kazakhstan, Kyrgyzstan, Romania, Russian Federation, Serbia, Turkey, and Ukraine).

Statistical analysis

Descriptive statistics were used, stratified by gender, to describe patients’ characteristics, the risk factor profile, and the information provided by health care professionals about patients’ risk factor control. Logistic regression analyses were performed adjusted for age at interview (continuous), history of stroke, history of heart failure, and self-reported diabetes. The association between gender and the risk factor profile was expressed as odds ratios (ORs) and their 95% confidence intervals (CIs). The threshold indicating statistical significance was set at P < 0.05. All statistical analyses were performed with IBM SPSS Statistics 25 software.

Results

Patient characteristics

Data from 8261 patients were available, of which 25.8% were women. On average, women were significantly older at the time of the study visit and had a lower educational level compared with men. Furthermore, women were more likely to have a history of stroke, a history of heart failure, and self-reported diabetes. Previous hospitalization for CABG or PCI was less frequent in women compared with men. In addition, patients recruited from middle-income countries were more often females. A detailed overview of the patient characteristics is given in Table 1.

Risk factor profile

Table 2 provides an overview of patients’ risk factor profile, stratified by gender. Overall, women were significantly more likely to be non-smokers. Also, the prevalence of smoking before the recruiting event was lower in women compared to men. No gender differences could be observed in smoking cessation. Interestingly, there is some indication that smoking behaviour differed across country income. A significant gender by country income interaction effect was found for smoking behaviour (P < 0.001). Stratification by country revealed a trend to significant gender differences in middle-income countries but not in high-income countries (Figure 1A). Furthermore, women were less likely to have adequate levels of physical activity. This finding was mostly consistent across countries (Figure 1B). Also, significant gender differences in disfavour of women were seen regarding the prevalence of non-obese patients. As shown in Figure 1C, gender differences in the prevalence of non-obese patients vary between countries. A significant gender by country income interaction effect was found for being non-obese (P = 0.001). Especially in middle-income countries, the odds of being non-obese are lower in women compared with men. Overall, no gender differences could be observed regarding blood pressure on target although gender differences varied substantially between counties (Figure 1D). Whereas no gender differences could be observed for treated hypertension (46.3% vs. 46.6%; P = 0.43), women were less likely to have uncontrolled hypertension (30.0% vs. 23.5%; P = 0.004). Interestingly, women were more likely to use anti-hypertensive medication (Table 2). Furthermore, women were less likely to have their LDL-C on target. Also, women were less likely to use lipid-lowering medication (Table 2). Both for treated (65.9% vs. 74.3%; P = 0.001) and untreated (85.4% vs. 91.8%; P < 0.001) patients, women were less likely to reach the LDL-C risk factor target. This pattern was quite homogeneous across countries (Figure 1E). Among patients with self-reported diabetes, women were less likely to reach the HbA1c level target. No gender differences could be observed in HbA1c level targets in patients without diabetes. Supplementary material online, Table S1 provides an overview of the combinations of risk factors. The combination of non-smoking, non-obese, and blood pressure on target was most common in both men and women.

Discussion

The importance of risk factor control in patients with CHD is widely documented.^13–15 However, previous research on risk factor management reported a large proportion of CHD patients who do not reach guidelines recommended risk factor targets, especially in female patients.^16,17 Overall, our study confirms previous study findings showing a worse risk factor control in female patients. Despite the fact that women smoked less, they were more likely to be physically inactive and a higher proportion of them were obese. Interestingly, no gender difference was observed in the control of blood pressure, although women used anti-hypertensive medication more often. Furthermore, LDL-C control was worse in women compared with men and women were less likely to use lipid-lowering drugs. Moreover, less women with diabetes reached the HbA1c target. Previous studies suggest that more comorbidities due to a later age of CHD onset in women and a possible lack of awareness among healthcare professionals and female patients concerning CHD in women resulting in delayed diagnosis, could partly explain this risk profile gender gap.^9,18 Several studies reported on gender differences in the risk factor management of CHD patients, in disfavour of women.^19–21 For instance, the VIRGO (Variation in recovery: Role of Gender on Outcomes of Young AMI Patients) study, including 3501 AMI patients, observed more diabetes and obesity in women compared with men.²² Also, the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in the Heart Disease Evaluated According to Recommended Therapies) registry, based on 51 620 AMI patients, reported on gender differences regarding blood pressure control and LDL-C targets, in disfavour of women.⁷ Moreover, the REACH Registry, based on 19 105 patients with documented arterial disease, reported that women were more likely to have elevated cholesterol levels and more women were obese.²³ Furthermore, the previous EUROASPIRE IV survey, conducted in 7998 coronary artery disease patients demonstrated that more women had a higher prevalence of obesity and they were less likely to have adequate levels of physical activity, LDL-C on target, and an HbA1c on target (in patients with self-reported diabetes).⁶ In an attempt to reduce these gender differences, several actions at the population level are taken to improve the awareness of CHD in female patients, such as ‘Go Red for Women’, an annual international awareness campaign initiated in 2004 to increase the awareness of CVD in women and which was endorsed by The World Heart Federation. The aim is to empower female patients to take charge of their own heart health.²⁴ Moreover, over 50 countries are running campaigns among healthcare professionals and the general public in order to increase the awareness of CVD in women.²⁴ Since individual behaviour is influenced by family, culture, and local policies, a population-wide strategy may be more successful in bridging the gender gap in cardiovascular disease burden.²

In continuation of previous research and the numerous awareness campaigns, the aim of this study was to provide a contemporary overview on potential gender differences in risk factor control in CHD patients, based on data from the most recent EUROASPIRE V survey. Despite several actions in order to reduce the CVD burden in women, our study results largely confirm previous research, showing substantial gender differences in the risk factor control of CHD patients. The implementation of the JES guidelines on risk factor target management in secondary prevention is suboptimal, especially in women. As reported in previous studies, women in this study were more likely to be non-smokers.^6,25 In this study, a remarkable gender difference was found. Analyses stratified by country revealed a trend to significant gender differences in middle-income countries but not in high-income countries. A possible explanation could be that there are increased smoking rates in female patients, especially in younger women from high-income countries.¹⁶ However, these results should be interpreted with caution because EUROASPIRE centres may be not representative for the entire country. Interestingly, no gender differences could be observed in smoking cessation. Moreover, women were more likely to be obese and have inadequate levels of physical activity. Also, women had a higher prevalence of self-reported diabetes and they were less likely to reach HbA1c level targets if having diabetes. Evidence suggests a growing burden of obesity, which may have an impact on other risk factors, such as raised blood pressure and diabetes.^4,26 It is possible that women were more likely to have diabetes due to the higher prevalence of obesity, which can partly explain these findings. Furthermore, women were less likely to reach LDL-C level targets. These findings are in line with the SURF (Survey of Risk Factors) study, based on 10 112 CHD patients (2012–13).⁸ A possible explanation could be that there is insufficient evidence about the effectiveness of evidence-based medications in women.^8,27 Evidence-based guidelines are based on large clinical trials, which are typically dominated by male participants.¹⁶ Interestingly, as shown in our study, women were less likely to use lipid-lowering medication at the time of the study visit. Previous research confirmed this findings, reporting that women were less likely to be treated with statins which can partly explain this gender difference in LDL-C control.⁷ Also, women are less likely to adhere to statins because of more side effects.²⁸ Similar to previous studies (EUROASPIRE IV, the VIRGO-study) no gender differences could be observed in the overall blood pressure control.^6,29 Remarkably, women were more likely than men to use anti-hypertensive medication at the time of the study visit.

It has to be underlined that previous EUROASPIRE analyses regarding gender differences in medical treatment revealed little to no gender differences.^6,30 The risk factor profile of female patients remains suboptimal. There are several possible explanations for the worse risk factor control in female patients diagnosed with CHD. First, as suggested in the INTERHEART study, women developed CHD on average 10 years later compared with men. Women may therefore have a lower risk factor burden at younger age.³¹ This might be partly explained by the protective effect of oestrogens.³² Due to the older age of onset, women may already have a worse risk factor profile before the recruiting event, which may result in a greater effort needed to bring them on target. Further research should focus on existing gender differences in primary prevention, which can explain this gender gap.^33,34 Moreover, research suggests that women were less likely to be told by a healthcare professional that they were at risk.²² In addition, women were more likely to have anxiety and depression, which were associated with a higher prevalence of risk factors like inadequate levels of physical activity and obesity.^35,36 This could be a possible explanation for the lower levels of physical activity and a higher prevalence of obesity in women.

A major strength of the EUROASPIRE surveys is that data are based on standardized methods and equipment, including central laboratory analyses. Therefore, we believe the EUROASPIRE V survey provides reliable information on the actual risk factor profile of coronary patients in Europe. Although our study provides an up to date overview on the risk factor control of CHD patients, some limitations should be mentioned. Not all geographical areas within each country were selected by the national principal investigators and may therefore not be representative for the entire country. The average EUROASPIRE V interview participation rate was low (56%). Non-participants may have a worse lifestyle and a poorer risk factor control.

Conclusion

In conclusion, although risk factor management is a major component in CHD care in both genders, our results suggest substantial gender differences for secondary prevention, mostly in disfavour of women. Despite the fact that previous EUROASPIRE findings suggest that there are only limited gender differences in the medical treatment of CHD patients, this was not reflected in their risk factor profile. Actions are needed to further elucidate this gender-differential in risk factor control.

Supplementary material

Supplementary material is available at European Journal of Preventive Cardiology online.

Acknowledgements

Registry Executive Committee and Steering Committee of the EURObservational Research Programme (EORP). Data collection was conducted by the EORP department from the ESC by Emanuela Fiorucci as Project Officer, Viviane Missiamenou, and Florian Larras as Data Manager. All investigators are listed in Supplementary material online, Appendix S1. The EUROASPIRE Study Group is grateful to the administrative staff, physicians, nurses and other personnel in the hospitals in which the survey was carried out and to all patients who participated in the surveys.

Funding

The EUROASPIRE V survey was carried out under the auspices of the European Society of Cardiology, EURObservational Research Programme (EORP). Since the start of EORP, the following companies have supported the programme: Amarin, Amgen, Daiichi Sankyo, Elli Lily, Ferrer, Novo Nordisk, Pfizer, and Sanofi. The sponsors of the EuroAspire surveys had no role in the design, data collection, data analysis, data interpretation, decision to publish, or writing the manuscript. P.V. is financially supported by the ‘Fonds voor Hartchirurgie—Fonds pour la Chirurgie Cardiaque’.

Conflict of interest: The authors declare that there is no conflict of interest.

References

Author notes